ID   ACEA_COCIM              Reviewed;         538 AA.
AC   Q96TP5; J3KKS8; Q1E625;
DT   11-OCT-2004, integrated into UniProtKB/Swiss-Prot.
DT   03-OCT-2006, sequence version 2.
DT   27-MAR-2024, entry version 98.
DE   RecName: Full=Isocitrate lyase {ECO:0000250|UniProtKB:P28240};
DE            Short=ICL {ECO:0000305};
DE            Short=Isocitrase {ECO:0000305};
DE            Short=Isocitratase {ECO:0000305};
DE            EC=4.1.3.1 {ECO:0000250|UniProtKB:P28240};
DE   AltName: Full=Methylisocitrate lyase {ECO:0000250|UniProtKB:P28240};
DE            Short=MICA {ECO:0000305};
DE            EC=4.1.3.30 {ECO:0000250|UniProtKB:P28240};
DE   AltName: Full=Threo-D(S)-isocitrate glyoxylate-lyase {ECO:0000305};
GN   Name=ICL1 {ECO:0000250|UniProtKB:P28240}; ORFNames=CIMG_01988;
OS   Coccidioides immitis (strain RS) (Valley fever fungus).
OC   Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Eurotiomycetes;
OC   Eurotiomycetidae; Onygenales; Onygenaceae; Coccidioides.
OX   NCBI_TaxID=246410;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA].
RA   Shi Q., Ivey F.D., Woitaske M.D., Magee D.M., Cox R.A.;
RT   "Cloning of isocitrate lyase of Coccidioides immitis.";
RL   Submitted (OCT-2001) to the EMBL/GenBank/DDBJ databases.
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=RS;
RX   PubMed=19717792; DOI=10.1101/gr.087551.108;
RA   Sharpton T.J., Stajich J.E., Rounsley S.D., Gardner M.J., Wortman J.R.,
RA   Jordar V.S., Maiti R., Kodira C.D., Neafsey D.E., Zeng Q., Hung C.-Y.,
RA   McMahan C., Muszewska A., Grynberg M., Mandel M.A., Kellner E.M.,
RA   Barker B.M., Galgiani J.N., Orbach M.J., Kirkland T.N., Cole G.T.,
RA   Henn M.R., Birren B.W., Taylor J.W.;
RT   "Comparative genomic analyses of the human fungal pathogens Coccidioides
RT   and their relatives.";
RL   Genome Res. 19:1722-1731(2009).
RN   [3]
RP   GENOME REANNOTATION.
RC   STRAIN=RS;
RX   PubMed=20516208; DOI=10.1101/gr.103911.109;
RA   Neafsey D.E., Barker B.M., Sharpton T.J., Stajich J.E., Park D.J.,
RA   Whiston E., Hung C.-Y., McMahan C., White J., Sykes S., Heiman D.,
RA   Young S., Zeng Q., Abouelleil A., Aftuck L., Bessette D., Brown A.,
RA   FitzGerald M., Lui A., Macdonald J.P., Priest M., Orbach M.J.,
RA   Galgiani J.N., Kirkland T.N., Cole G.T., Birren B.W., Henn M.R.,
RA   Taylor J.W., Rounsley S.D.;
RT   "Population genomic sequencing of Coccidioides fungi reveals recent
RT   hybridization and transposon control.";
RL   Genome Res. 20:938-946(2010).
CC   -!- FUNCTION: Catalyzes the formation of succinate and glyoxylate from
CC       isocitrate, a key step of the glyoxylate cycle, which operates as an
CC       anaplerotic route for replenishing the tricarboxylic acid cycle.
CC       Required for growth on ethanol or acetate, but dispensable when
CC       fermentable carbon sources are available. Acts also on 2-
CC       methylisocitrate. {ECO:0000250|UniProtKB:P28240}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=D-threo-isocitrate = glyoxylate + succinate;
CC         Xref=Rhea:RHEA:13245, ChEBI:CHEBI:15562, ChEBI:CHEBI:30031,
CC         ChEBI:CHEBI:36655; EC=4.1.3.1;
CC         Evidence={ECO:0000250|UniProtKB:P28240};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=(2S,3R)-3-hydroxybutane-1,2,3-tricarboxylate = pyruvate +
CC         succinate; Xref=Rhea:RHEA:16809, ChEBI:CHEBI:15361,
CC         ChEBI:CHEBI:30031, ChEBI:CHEBI:57429; EC=4.1.3.30;
CC         Evidence={ECO:0000250|UniProtKB:P28240};
CC   -!- COFACTOR:
CC       Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC         Evidence={ECO:0000250|UniProtKB:P9WKK7};
CC   -!- PATHWAY: Carbohydrate metabolism; glyoxylate cycle; (S)-malate from
CC       isocitrate: step 1/2.
CC   -!- SUBUNIT: Homotetramer. {ECO:0000250|UniProtKB:P28240}.
CC   -!- SUBCELLULAR LOCATION: Glyoxysome {ECO:0000250|UniProtKB:P28299}.
CC   -!- SIMILARITY: Belongs to the isocitrate lyase/PEP mutase superfamily.
CC       Isocitrate lyase family. {ECO:0000305}.
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DR   EMBL; AF420484; AAL16915.1; -; Genomic_DNA.
DR   EMBL; AY038602; AAK72548.2; -; mRNA.
DR   EMBL; GG704911; EAS36634.3; -; Genomic_DNA.
DR   RefSeq; XP_001248217.1; XM_001248216.2.
DR   AlphaFoldDB; Q96TP5; -.
DR   SMR; Q96TP5; -.
DR   STRING; 246410.Q96TP5; -.
DR   GeneID; 4567087; -.
DR   KEGG; cim:CIMG_01988; -.
DR   VEuPathDB; FungiDB:CIMG_01988; -.
DR   InParanoid; Q96TP5; -.
DR   OMA; YVSGWQV; -.
DR   OrthoDB; 983054at2759; -.
DR   UniPathway; UPA00703; UER00719.
DR   Proteomes; UP000001261; Unassembled WGS sequence.
DR   GO; GO:0009514; C:glyoxysome; IEA:UniProtKB-SubCell.
DR   GO; GO:0004451; F:isocitrate lyase activity; IEA:UniProtKB-EC.
DR   GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR   GO; GO:0046421; F:methylisocitrate lyase activity; IEA:UniProtKB-EC.
DR   GO; GO:0006097; P:glyoxylate cycle; IEA:UniProtKB-UniPathway.
DR   GO; GO:0006099; P:tricarboxylic acid cycle; IEA:UniProtKB-KW.
DR   Gene3D; 1.10.10.850; -; 1.
DR   Gene3D; 3.20.20.60; Phosphoenolpyruvate-binding domains; 1.
DR   InterPro; IPR006254; Isocitrate_lyase.
DR   InterPro; IPR018523; Isocitrate_lyase_ph_CS.
DR   InterPro; IPR015813; Pyrv/PenolPyrv_Kinase-like_dom.
DR   InterPro; IPR040442; Pyrv_Kinase-like_dom_sf.
DR   NCBIfam; TIGR01346; isocit_lyase; 1.
DR   PANTHER; PTHR21631:SF3; BIFUNCTIONAL GLYOXYLATE CYCLE PROTEIN; 1.
DR   PANTHER; PTHR21631; ISOCITRATE LYASE/MALATE SYNTHASE; 1.
DR   Pfam; PF00463; ICL; 1.
DR   PIRSF; PIRSF001362; Isocit_lyase; 1.
DR   SUPFAM; SSF51621; Phosphoenolpyruvate/pyruvate domain; 1.
DR   PROSITE; PS00161; ISOCITRATE_LYASE; 1.
PE   2: Evidence at transcript level;
KW   Glyoxylate bypass; Glyoxysome; Lyase; Magnesium; Metal-binding; Peroxisome;
KW   Reference proteome; Tricarboxylic acid cycle.
FT   CHAIN           1..538
FT                   /note="Isocitrate lyase"
FT                   /id="PRO_0000068788"
FT   ACT_SITE        207
FT                   /note="Proton acceptor"
FT                   /evidence="ECO:0000250|UniProtKB:P9WKK7"
FT   BINDING         98..100
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250|UniProtKB:P9WKK7"
FT   BINDING         169
FT                   /ligand="Mg(2+)"
FT                   /ligand_id="ChEBI:CHEBI:18420"
FT                   /evidence="ECO:0000250|UniProtKB:P9WKK7"
FT   BINDING         208..209
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250|UniProtKB:P9WKK7"
FT   BINDING         244
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250|UniProtKB:P9WKK7"
FT   BINDING         424..428
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250|UniProtKB:P9WKK7"
FT   BINDING         458
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250|UniProtKB:P9WKK7"
FT   CONFLICT        272
FT                   /note="N -> T (in Ref. 1; AAK72548/AAL16915)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        328..329
FT                   /note="AI -> TT (in Ref. 1; AAK72548/AAL16915)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        522
FT                   /note="V -> I (in Ref. 1; AAK72548/AAL16915)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   538 AA;  60383 MW;  CD722C99DB39502C CRC64;
     MSLSVEQEEQ KYWEEVEAVK QWWKDSRWRY TKRPFTAEQI VAKRGNLKIE YPSNVQSKKL
     WKLVEEKFKT KTASFTYGCL DPTMVTQMVK YLDTVYVSGW QSSSTASSTD EPSPDLADYP
     MNTVPNKVNQ LWMAQLFHDR KQREERLRNP KEKRASLANI DYLAPIIADA DTGHGGLTAV
     MKLTKLFIER GAAGIHIEDQ APGTKKCGHM AGKVLVPISE HINRLVAIRA QADIMGTDLL
     AIARTDSEAA TLITSTIDPR DHAFVVGSTN PNLEPLNDLM IAAERAGKNG AELQAIEDSW
     TAKAGLKRFE DAVIDQIKAS SAANKQAAID AFLREIKGKS NKEARAIARQ ILGTDIFWDW
     DAPRTREGYY RYQGGCQCAI NRAVAFAPFA DLIWMESKLP DYAQAKEFAE GVHAVWPQQK
     LAYNLSPSFN WKAAMPRDEQ ETYIRRLGEL GYCWQFITLA GLHTTALISD QFAKAYAKQG
     MRAYGELVQE PEMENKVDVV THQKWSGANY VDELLKMVTG GVSSTSAMGK GVTEDQFK
//